Objective To explore the expression of long non-coding RNA (LncRNA) KCNQ1OT1 and its clinical significance in non-small cell lung cancer (NSCLC). Methods Eighty-nine NSCLC patients who underwent surgery were recruited in Sichuan Cancer Hospital from January 2011 to December 2013. Quantitative real-time PCR was used to detect the expression of LncRNA KCNQ1OT1 in tumor tissues and paracarcinoma tissues (5cm or above away from tumor). The relationship between LncRNA KCNQ1OT1 expression and clinicopathologic features was analyzed by univariate analysis and Cox regression analysis. Results The expression of LncRNA KCNQ1OT1 significantly increased in tumor tissues than that in paracarcinoma tissues (P < 001). The patients were divided into a high expression group and a low expression group according to the relative expression of LncRNA KCNQ1OT1. Univariate analysis showed that the differences between two groups were not significant in age, gender or histological type, but were significant in tumor size (χ2=12.619, P < 001), lymph node metastasis(χ2=10.298, P=0.001), TNM stage(χ2=7.199, P=0.007), and history of smoking(χ2=24.005, P < 001). Kaplan-Meier analysis showed the patients with high LncRNA KCNQ1OT1 expression had significantly lower overall survival time (20.0 months vs. 35.0 months, χ2=45.860, P < 001) and significantly lower progression-free survival time (12.0 months vs. 24.0 months, χ2=31.510, P < 001) than those with low LncRNA KCNQ1OT1 expression. Cox regression analysis revealed that the disease stage and the expression of LncRNA KCNQ1OT1 could be used as independent prognostic markers for poor prognosis. Conclusion LncRNA KCNQ1OT1 is highly expressed in tumor tissues and associated with the prognosis of NSCLC patients, thus can be used as a potential marker for predicting the prognosis of lung cancer.